New obstacles to the control of rabies

The epidemiology of rabies has changed over the past few years. Although the control and elimination of rabies among non-flying terrestrial mammals have been achieved in the countries of Western Europe, the incidence of rabies is rising in other regions of the world, due to inadequate public health measures. Furthermore, lyssaviruses, like all RNA viruses, are able to evolve rapidly and adapt to new animal species. Numerous lyssavirus variants have been characterised recently. These new variants pose new public health risks and hamper rabies elimination strategies.La rage est une encéphalite induite par des virus appartenant au genre Lyssavirus et son épidémiologie a changé durant ces dernières années. Alors que le contrôle et l'élimination de la rage des mammifères terrestres non volants ont été achevés dans les pays d'Europe de l'ouest, l'incidence de la rage augmente dans certaines régions du monde du fait de la faiblesse des mesures de santé publique mises en place. De plus, les lyssavirus ont la capacité, comme les autres virus dont le génome est constitué d'ARN, d'évoluer rapidement et de s'adapter à de nouvelles espèces animales. Ainsi de nombreux variants de lyssavirus ont été caractérisés récemment. Ces nouveaux variants font peser de nouveaux risques sur la santé publique et compliquent les stratégies d'élimination de la rage

Recent developments of the epidemiology of lyssavirus infections and consequences for humans

The epidemiology of rabies has changed during the recent years. The control and the elimination of rabies in autochtonous terrestrial non flying animals has been achieved in West European countries. However, emerging or re-emerging lyssavirus variants have been identified and lead to the developments of unexpected and unassessed risks for public health. This raised new interogations concerning the future of the methods used for controling rabies in the field of diagnosis, prophylaxis and identification of new lyssavirus variants.L’épidémiologie de la rage a changé durant ces dernières années. Le contrôle et l’élimination de la rage des animaux terrestres non volants ont été atteints dans les pays d’Europe de l’ouest. Cependant, de nouveaux variants isolés de part le monde font peser de nouveaux risques sur la santé publique. Ceci soulève de nouvelles interrogations concernant l’évolution nécessaire des méthodes de contrôle de la rage, en particulier dans les secteurs du diagnostic, de l’identification et de la prophylaxie des nouveaux variants de lyssavirus

Seroprevalence Dynamics of European Bat Lyssavirus Type 1 in a Multispecies Bat Colony

We report an active surveillance study of the occurrence of specific antibodies to European Bat Lyssavirus Type 1 (EBLV-1) in bat species, scarcely studied hitherto, that share the same refuge. From 2004 to 2012, 406 sera were obtained from nine bat species. Blood samples were subjected to a modified fluorescent antibody virus neutralization test to determine the antibody titer. EBLV-1-neutralizing antibodies were detected in six of the nine species analyzed (Pipistrellus pipistrellus, P. kuhlii, Hypsugo savii, Plecotus austriacus, Eptesicus serotinus and Tadarida teniotis). Among all bats sampled, female seroprevalence (20.21%, 95% CI: 14.78%-26.57%) was not significantly higher than the seroprevalence in males (15.02%, 95% CI: 10.51%-20.54%). The results showed that the inter-annual variation in the number of seropositive bats in T. teniotis and P. austriacus showed a peak in 2007 (>70% of EBLV-1 prevalence). However, significant differences were observed in the temporal patterns of the seroprevalence modeling of T. teniotis and P. austriacus. The behavioral ecology of these species involved could explain the different annual fluctuations in EBLV-1 seroprevalence

European Bat Lyssavirus Infection in Spanish Bat Populations

From 1992 to 2000, 976 sera, 27 blood pellets, and 91 brains were obtained from 14 bat species in 37 localities in Spain. Specific anti-European bat lyssavirus 1 (EBL1)-neutralizing antibodies have been detected in Myotis myotis, Miniopterus schreibersii, Tadarida teniotis, and Rhinolophus ferrumequinum in the region of Aragon and the Balearic Islands. Positive results were also obtained by nested reverse transcription-polymerase chain reaction on brain, blood pellet, lung, heart, tongue, and esophagus-larynx-pharynx of M. myotis, Myotis nattereri, R. ferrumequinum, and M. schreibersii. Determination of nucleotide sequence confirmed the presence of EBL1 RNA in the different tissues. In one colony, the prevalence of seropositive bats over time corresponded to an asymmetrical curve, with a sudden initial increase peaking at 60% of the bats, followed by a gradual decline. Banded seropositive bats were recovered during several years, indicating that EBL1 infection in these bats was nonlethal. At least one of this species (M. schreibersii) is migratory and thus could be partially responsible for the dissemination of EBL1 on both shores of the Mediterranean Sea

Validation of a Rapid Rabies Diagnostic Tool for Field Surveillance in Developing Countries

One root cause of the neglect of rabies is the lack of adequate diagnostic tests in the context of low income countries. A rapid, performance friendly and low cost method to detect rabies virus (RABV) in brain samples will contribute positively to surveillance and consequently to accurate data reporting, which is presently missing in the majority of rabies endemic countries.; We evaluated a rapid immunodiagnostic test (RIDT) in comparison with the standard fluorescent antibody test (FAT) and confirmed the detection of the viral RNA by real time reverse transcription polymerase chain reaction (RT-qPCR). Our analysis is a multicentre approach to validate the performance of the RIDT in both a field laboratory (N'Djamena, Chad) and an international reference laboratory (Institut Pasteur, Paris, France). In the field laboratory, 48 samples from dogs were tested and in the reference laboratory setting, a total of 73 samples was tested, representing a wide diversity of RABV in terms of animal species tested (13 different species), geographical origin of isolates with special emphasis on Africa, and different phylogenetic clades. Under reference laboratory conditions, specificity was 93.3% and sensitivity was 95.3% compared to the gold standard FAT test. Under field laboratory conditions, the RIDT yielded a higher reliability than the FAT test particularly on fresh and decomposed samples. Viral RNA was later extracted directly from the test filter paper and further used successfully for sequencing and genotyping.; The RIDT shows excellent performance qualities both in regard to user friendliness and reliability of the result. In addition, the test cassettes can be used as a vehicle to ship viral RNA to reference laboratories for further laboratory confirmation of the diagnosis and for epidemiological investigations using nucleotide sequencing. The potential for satisfactory use in remote locations is therefore very high to improve the global knowledge of rabies epidemiology. However, we suggest some changes to the protocol, as well as careful further validation, before promotion and wider use

Serologic Evidence of Lyssavirus Infection in Bats, Cambodia

In Cambodia, 1,303 bats of 16 species were tested for lyssavirus. No lyssavirus nucleocapsid was detected in 1,283 brains tested by immunofluorescence assay. Antibodies against lyssaviruses were detected by enzyme-linked immunosorbent assay in 144 (14.7%) of 981 serum samples. Thirty of 187 serum samples contained neutralizing antibodies against different lyssaviruses

Laboratory Surveillance of Rabies in Humans, Domestic Animals, and Bats in Madagascar from 2005 to 2010

Background. Rabies virus (RABV) has circulated in Madagascar at least since the 19th century. Objectives. To assess the circulation of lyssavirus in the island from 2005 to 2010. Materials and Methods. Animal (including bats) and human samples were tested for RABV and other lyssavirus using antigen, ribonucleic acid (RNA), and antibodies detection and virus isolation. Results. Half of the 437 domestic or tame wild terrestrial mammal brains tested were found RABV antigen positive, including 54% of the 341 dogs tested. This percentage ranged from 26% to 75% across the period. Nine of the 10 suspected human cases tested were laboratory confirmed. RABV circulation was confirmed in 34 of the 38 districts sampled. No lyssavirus RNA was detected in 1983 bats specimens. Nevertheless, antibodies against Lagos bat virus were detected in the sera of 12 among 50 Eidolon dupreanum specimens sampled. Conclusion. More than a century after the introduction of the vaccine, rabies still remains endemic in Madagascar

Ecological Factors Associated with European Bat Lyssavirus Seroprevalence in Spanish Bats.

Bats have been proposed as major reservoirs for diverse emerging infectious viral diseases, with rabies being the best known in Europe. However, studies exploring the ecological interaction between lyssaviruses and their natural hosts are scarce. This study completes our active surveillance work on Spanish bat colonies that began in 1992. Herein, we analyzed ecological factors that might affect the infection dynamics observed in those colonies. Between 2001 and 2011, we collected and tested 2,393 blood samples and 45 dead bats from 25 localities and 20 bat species. The results for dead confirmed the presence of EBLV-1 RNA in six species analyzed (for the first time in Myotis capaccinii). Samples positive for European bat lyssavirus-1 (EBLV-1)-neutralizing antibodies were detected in 68% of the localities sampled and in 13 bat species, seven of which were found for the first time (even in Myotis daubentonii, a species to date always linked to EBLV-2). EBLV-1 seroprevalence (20.7%) ranged between 11.1 and 40.2% among bat species and seasonal variation was observed, with significantly higher antibody prevalence in summer (July). EBLV-1 seroprevalence was significantly associated with colony size and species richness. Higher seroprevalence percentages were found in large multispecific colonies, suggesting that intra- and interspecific contacts are major risk factors for EBLV-1 transmission in bat colonies. Although bat-roosting behavior strongly determines EBLV-1 variability, we also found some evidence that bat phylogeny might be involved in bat-species seroprevalence. The results of this study highlight the importance of life history and roost ecology in understanding EBLV-1-prevalence patterns in bat colonies and also provide useful information for public health officials

Insights into Persistence Mechanisms of a Zoonotic Virus in Bat Colonies Using a Multispecies Metapopulation Model.

Rabies is a worldwide zoonosis resulting from Lyssavirus infection. In Europe, Eptesicus serotinus is the most frequently reported bat species infected with Lyssavirus, and thus considered to be the reservoir of European bat Lyssavirus type 1 (EBLV-1). To date, the role of other bat species in EBLV-1 epidemiology and persistence remains unknown. Here, we built an EBLV-1−transmission model based on local observations of a three-cave and four-bat species (Myotis capaccinii, Myotis myotis, Miniopterus schreibersii, Rhinolophus ferrumequinum) system in the Balearic Islands, for which a 1995-2011 serological dataset indicated the continuous presence of EBLV-1. Eptesicus serotinus was never observed in the system during the 16-year follow-up and therefore was not included in the model. We used the model to explore virus persistence mechanisms and to assess the importance of each bat species in the transmission dynamics. We found that EBLV-1 could not be sustained if transmission between M. schreibersii and other bat species was eliminated, suggesting that this species serves as a regional reservoir. Global sensitivity analysis using Sobol's method revealed that following the rate of autumn−winter infectious contacts, M. schreibersii's incubation- and immune-period durations, but not the infectious period length, were the most relevant factors driving virus persistence